PTEN deletion enhances the regenerative ability of adult corticospinal neurons.
Nat Neurosci
; 13(9): 1075-81, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20694004
ABSTRACT
Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. We found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons. After development, the regrowth potential of CST axons was lost and this was accompanied by a downregulation of mTOR activity in corticospinal neurons. Axonal injury further diminished neuronal mTOR activity in these neurons. Forced upregulation of mTOR activity in corticospinal neurons by conditional deletion of Pten, a negative regulator of mTOR, enhanced compensatory sprouting of uninjured CST axons and enabled successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possessed the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tratos Piramidais
/
PTEN Fosfo-Hidrolase
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Regeneração Nervosa
/
Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article